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Programmable Enzymatic Synthesis of Bioactive Compounds

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  • Full or part time
    Prof S Flitsch
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

The aim of this project is to devise a conceptually novel and general platform that will deliver a step-change in complexity of de novo biosynthetic pathways by moving from manual to automated design, build and test. We have identified three bottlenecks that will need to be overcome to build an effective ProgES platform i. Increasing the diversity of structures accessible through biocatalysis by incorporation of C-H activation for early and late stage functionalisation. ii. Fast analytical methods to improve throughput and timescale. iii. A dedicated bioinformatics platform that can harness the technology already developed for chemical and biochemical synthesis and incorporate them into an effective tool for automation for de novo biosynthesis. As proof of principle the ProgrES platform will be used to generate a diverse library of imino sugars of unprecedented complexity.

Contact for further Information: Professor Sabine Flitsch [Email Address Removed]

Full details on how to apply can be found here: http://www.chemistry.manchester.ac.uk/study/postgraduate/researchdegrees/howtoapply/

Funding Notes

The position is available from September 2018, funded by an ERC Advanced Grant which covers tuition fees and stipend for 4 years Applications are invited from UK/EU nationals. Candidates from outside the UK must have resided in the UK for 3 years prior to commencing the PhD to be eligible to apply.

Applicants are expected to hold, or be about to obtain, a minimum upper second class undergraduate degree (or equivalent) in chemistry, biochemistry or a related science. A Masters degree in a relevant subject and/or experience in bioinformatics or biocatalysis is desirable.

References

France, Scott P; Hepworth, Lorna J; Turner, Nicholas J; Flitsch, Sabine L; “Constructing Biocatalytic Cascades: In Vitro and in Vivo Approaches to de Novo Multi-Enzyme Pathways.” ACS Catal., 2017, 7(1), 710-724. DOI: 10.1021/acscatal.6b02979

France, Scott P.; Hussain, Shahed; Hill, Andrew M.; Hepworth, Lorna J.; Howard, Roger M.; Mulholland, Keith R.; Flitsch, Sabine L.; Turner, Nicholas J. “One-Pot Cascade Synthesis of Mono- and Disubstituted Piperidines and Pyrrolidines using Carboxylic Acid Reductase (CAR), ω-Transaminase (ω-TA), and Imine Reductase (IRED) Biocatalysts”. ACS Catalysis (2016), 6(6), 3753-3759. DOI:10.1021/acscatal.6b00855

Hepworth, Lorna; France, Scott; Hussain, Shahed; Both, Peter; Turner, Nicholas; Flitsch, Sabine. De Novo Enzyme Cascades in Whole Cells for the Synthesis of Chiral Cyclic Amines.” ACS Catalysis, 2017, 7, 2920-2925. DOI: 10.1021/acscatal.7b00513

Sardzik, Robert; Green, Anthony P.; Laurent, Nicolas; Both, Peter; Fontana, Carolina; Voglmeir, Josef; Weissenborn, Martin J.; Haddoub, Rose; Grassi, Paola; Haslam, Stuart M.; Widmalm, Goran; Flitsch, Sabine L. “Chemoenzymatic Synthesis of O-Mannosylpeptides in Solution and on Solid Phase” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 134(10); 4521 – 4524. DOI 10.1021/ja211861m – MAR 14 2012

Both, H. Busch, P. Kelly, F. G. Mutti, N. J. Turner, S. L. Flitsch, Sabine J. “Whole-Cell Biocatalysts for Stereoselective C-H Amination Reactions”. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION., 55; 1511 – 1513.DOI: 10.1002/anie.201510028– JAN 22 2016


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